César Milstein

About César Milstein
César Milstein (8 October 1927 – 24 March 2002) was an Argentine biochemist in the field of antibody research. Milstein shared the Nobel Prize in Physiology or Medicine in 1984 with Niels K. Jerne and Georges Köhler.Biography
Milstein was born in Bahía Blanca, Argentina. He graduated from the University of Buenos Aires and obtained a PhD under Professor Stoppani (Professor of Biochemistry) in the Medical School on kinetic studies with the enzyme aldehyde dehydrogenase. In 1958, funded by the British Council, he joined the Biochemistry Department at the University of Cambridge to work for a PhD under Malcolm Dixon on the mechanism of metal activation of the enzyme phosphoglucomutase. During this work he collaborated with Frederick Sanger whose group he joined with a short-term Medical Research Council appointment.
Career
The major part of Milstein's research career was devoted to studying the structure of antibodies and the mechanism by which antibody diversity is generated. It was as part of this quest that in 1975 he, together with Georges Köhler (a postdoctoral fellow in his laboratory), developed the hybridoma technique for the production of monoclonal antibodies—a discovery recognised by the award of the 1984 Nobel Prize for Physiology or Medicine. This discovery led to an enormous expansion in the exploitation of antibodies in science and medicine. The monoclonal antibody experiment was the control experiment to one suggested by Prof.Pieczenik, which is known as the Cotton-Milstein experiment. This was the fusion of two known myeloma cells with defined constant and variable regions to identify at which level the recombination of coding occurred i.e. nucleotide or protein. This experiment is a variation of the Zinder-Edelman experiment where they dissociated immunoglobulin heavy and light chains produced against f1 and f2 bacteriophage. They then created heteroduplexes of these light and heavy chains to identify antibody binding specificity. Heteroduplexes do not bind properly. This has enormous consequences on interpreting the combinatorial phage libraries being commercially produced presently.

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